Transmission of mouse hepatitis virus (MHV) was studied in a "natural" animal room setting using euthymic and athymic mice; and in unnatural settings where experimentally infected cage mates served as time-controlled donors. "Natural" setting. Euthymic sentinel CD-1 mice placed in nonfilter capped cages in animal rooms suspected of harboring endemic MHV were examined at intervals for seroconversion to MHV by the ELISA method. First results of serological tests produced a mixture of non converters and low reading converters, making interpretation difficult or uncertain. Athymic sentinels killed at the same time points and examined for evidence of MHV infection had histological criteria that predicted insipient characteristic lesions at 7 and 11 weeks post placement. At 13 and 17 weeks athymic mice had fully developed MHV lesions. The length of time necessary for lesions to develop in athymic mice is difficult to predict but the sensitivity of system appears to be of a high order. Unnatural setting. CD-1 weanling mice were experimentally infected with MHV by the i.p. and oral routes. Beginning at 3 dys PI these mice were placed in sterile cages and cohabited with uninoculated CD-1 weanlings known to be free of MHV infection. Cohabitants were removed after three days and replaced by new virus free weanlings. This procedure was repeated with seven groups of cohabitants. The last group of cohabitants was allowed to remain with the infected mice for 7 days (21-28 days PI). Upon removal from infected mice, each group of cohabitants was isolated in a Horsfall unit for 28 days, then bled for serological examination. A second cohort of virus free weanlings was inoculated orally with a slurry of feces collected each time cohabitants were removed from infected mice. Only the virus free weanlings exposed to infected mice between 12-15 and 15-18 days PI and mice inoculated with slurry from these same time points seroconverted positive for MHV. No other groups or slurry cohorts seroconverted.